Transplantation of novel human GDF5-expressing CHO cells is neuroprotective in models of Parkinson's disease

Growth/differentiation factor 5 (GDF5) is a neurotrophic factor that promotes the survival of midbrain dopaminergic neurons in vitro and in vivo and as such is potentially useful in the treatment of Parkinson's disease (PD). This study shows that a continuous supply of GDF5, produced by transplanted GDF5-overexpressing CHO cells in vivo, has neuroprotective and neurorestorative effects on midbrain dopaminergic neurons following 6-hydroxydopamine (6-OHDA)-induced lesions of the adult rat nigrostriatal pathway. It also increases the survival and improves the function of transplanted embryonic dopaminergic neurons in the 6-OHDA-lesioned rat model of PD. This study provides the first proof-of-principle that sustained delivery of GDF5 in vivo may be useful in the treatment of PD

Time-Domain and Spectral-Domain Optical Coherence Tomography of Retinal Nerve Fiber Layer in MS Patients and Healthy Controls

Objective. The aim of this study was to compare retinal nerve fiber layer thickness (RNFLT) between spectral-domain (SD-) and time-domain optical coherence tomography (TD-OCT) in MS patients and healthy controls (HC). Furthermore, RNFLT between MS eyes with and without optic neuritis (ON) and HC should be explored. Finally, the relationship between RNFLT, disease duration, EDSS, and disease modifying therapy (DMT) should be established. Design. Prospective, cross-sectional study. Participants. 28 MS patients and 35 HC. Methods. Both groups underwent TD- and SD-OCT measurements. RFNLT was correlated between the two machines and between MS eyes with and without ON and HC. Furthermore, RNFLT was correlated to disease duration, EDSS and DMT. Results. A strong correlation (Pearson's r = 0.921, P < 0.001), but a statistically significant difference of 2 μm (P < 0.001), was found between the two devices. RNFLT was significantly different between MS eyes with history of ON (mean RFNLT (SD) 72.21 μm (15.83 μm)), MS eyes without history of ON 93.03 μm (14.25 μm), and HC 99.07 μm (7.23 μm) (P < 0.001). Conclusions. The measurements between different generation of OCT machines are not interchangeable, which should be taken into account if comparing results between different machines and switching OCT machine in longitudinal studies

Editorial: Ireland’s online learning call

The editorial board of the Irish Journal of Technology Enhanced Learning (IJTEL) would like to use this opportunity to thank each and every one of you working through a very challenging time over the past twelve months of the pandemic. It is a significant event, a critical incident, that will take some time to document and reflect upon in future journal editions. So many words have already been written about this past year that try to capture the disruption and change. However, to summarise even a scintilla of what has happened across Irish higher education is a slightly daunting prospect. We have seen various terms used to describe the rapid shift to teaching and learning online, such as milestone, pivot, emergency remote teaching. None of these fully encompass the myriad of ways that those of us working in education have had to become resilient, responsive, and supportive of colleagues during this period. Considering the response from members of the educational technology community within Ireland, one could argue that the term overwhelming is a good starting point. For a start, a tsunami of work ensued, that at times threatened to engulf individuals. Education ‘pivoted’ from a position where online was generally a supplementary or complementary activity to one where, in an online mode, we became the campus. Systems and processes were hastily altered, modified or expanded far beyond anybody’s expectations. While some of those have creaked and groaned, we have managed to teach classes, run meetings and carry out assessments; run on-campus labs and social distanced teaching; in short, we have kept going. People have been inventive, innovative and extremely hard working. But above all else, they have been generous; generous with their time, their expertise and generous in spirit

Symptoms in first degree relatives of patients with rheumatoid arthritis:evaluation of cross-sectional data from the symptoms in persons at risk of rheumatoid arthritis (SPARRA) questionnaire in the PRe-clinical EValuation of Novel Targets in RA (PREVeNT-RA) Cohort

Abstract Background First-degree relatives (FDRs) of people with rheumatoid arthritis (RA) have a fourfold increased risk of developing RA. The Symptoms in Persons At Risk of Rheumatoid Arthritis (SPARRA) questionnaire was developed to document symptoms in persons at risk of RA. The aims of this study were (1) to describe symptoms in a cohort of FDRs of patients with RA overall and stratified by seropositivity and elevated CRP and (2) to determine if patient characteristics were associated with symptoms suggestive of RA. Methods A cross-sectional study of FDRs of patients with RA, in the PREVeNT-RA study, who completed a study questionnaire, provided a blood sample measured for rheumatoid factor, anti-CCP and CRP and completed the SPARRA questionnaire. Moderate/severe symptoms and symmetrical, small and large joint pain were identified and described. Symptoms associated with both seropositivity and elevated CRP were considered suggestive of RA. Logistic regression was used to determine if symptoms suggestive of RA were associated with patient characteristics. Results Eight hundred seventy participants provided all data, 43 (5%) were seropositive and 122 (14%) had elevated CRP. The most frequently reported symptoms were sleep disturbances (20.3%) and joint pain (17.9%). Symmetrical and small joint pain were 11.3% and 12.8% higher, respectively, in those who were seropositive and 11.5% and 10.7% higher in those with elevated CRP. In the logistic regression model, seropositivity, older age and feeling depressed were associated with increased odds of small and symmetrical joint pain. Conclusions This is the first time the SPARRA questionnaire has been applied in FDRs of patients with RA and has demonstrated that the presence of symmetrical and small joint pain in this group may be useful in identifying people at higher risk of developing RA

No effect of New Zealand blackcurrant extract on recovery of muscle damage following running a half-marathon

New Zealand blackcurrant (NZBC) contains anthocyanins, known to moderate blood flow and display anti-inflammatory properties that may improve recovery from exercise-induced muscle damage. The authors examined whether NZBC extract supplementation enhances recovery from exercise-induced muscle damage after a half-marathon race. Following a randomized, double-blind, independent groups design, 20 (eight women) recreational runners (age 30 ± 6 years, height 1.73 ± 0.74 m, body mass 68.5 ± 7.8 kg, half-marathon finishing time 1:56:33 ± 0:18:08 hr:min:s) ingested either two 300-mg/day capsules of NZBC extract (CurraNZ™) or a visually matched placebo, for 7 days prior to and 2 days following a half-marathon. Countermovement jump performance variables, urine interleukin-6, and perceived muscle soreness and fatigue were measured pre, post, and at 24 and 48 hr after the half-marathon and analyzed using a mixed linear model with statistical significance set a priori at p  .05). Urine interleukin-6 increased 48-hr post-half-marathon in the NZBC group only (p  .05). Perceived muscle soreness and fatigue increased immediately post-half-marathon (p  .05). Supplementation with NZBC extract had no effect on the recovery of countermovement jump variables and perceptions of muscle soreness or fatigue following a half-marathon in recreational runners

Nrf2 is overexpressed in pancreatic cancer: implications for cell proliferation and therapy

<p>Abstract</p> <p>Background</p> <p>Nrf2 is a key transcriptional regulator of a battery of genes that facilitate phase II/III drug metabolism and defence against oxidative stress. Nrf2 is largely regulated by Keap1, which directs Nrf2 for proteasomal degradation. The Nrf2/Keap1 system is dysregulated in lung, head and neck, and breast cancers and this affects cellular proliferation and response to therapy. Here, we have investigated the integrity of the Nrf2/Keap1 system in pancreatic cancer.</p> <p>Results</p> <p>Keap1, Nrf2 and the Nrf2 target genes AKR1c1 and GCLC were detected in a panel of five pancreatic cancer cell lines. Mutation analysis of <it>NRF2 </it>exon 2 and <it>KEAP1 </it>exons 2-6 in these cell lines identified no mutations in <it>NRF2 </it>and only synonomous mutations in <it>KEAP1</it>. RNAi depletion of Nrf2 caused a decrease in the proliferation of Suit-2, MiaPaca-2 and FAMPAC cells and enhanced sensitivity to gemcitabine (Suit-2), 5-flurouracil (FAMPAC), cisplatin (Suit-2 and FAMPAC) and gamma radiation (Suit-2). The expression of Nrf2 and Keap1 was also analysed in pancreatic ductal adenocarcinomas (n = 66 and 57, respectively) and matching normal benign epithelium (n = 21 cases). Whilst no significant correlation was seen between the expression levels of Keap1 and Nrf2 in the tumors, interestingly, Nrf2 staining was significantly greater in the cytoplasm of tumors compared to benign ducts (P < 0.001).</p> <p>Conclusions</p> <p>Expression of Nrf2 is up-regulated in pancreatic cancer cell lines and ductal adenocarcinomas. This may reflect a greater intrinsic capacity of these cells to respond to stress signals and resist chemotherapeutic interventions. Nrf2 also appears to support proliferation in certain pancreatic adenocarinomas. Therefore, strategies to pharmacologically manipulate the levels and/or activity of Nrf2 may have the potential to reduce pancreatic tumor growth, and increase sensitivity to therapeutics.</p

The effect of providing feedback on inhaler technique and adherence from an electronic audio recording device, INCA®, in a community pharmacy setting: study protocol for a randomised controlled trial.

BACKGROUND: Poor adherence to inhaled medication may lead to inadequate symptom control in patients with respiratory disease. In practice it can be difficult to identify poor adherence. We designed an acoustic recording device, the INCA® (INhaler Compliance Assessment) device, which, when attached to an inhaler, identifies and records the time and technique of inhaler use, thereby providing objective longitudinal data on an individual\u27s adherence to inhaled medication. This study will test the hypothesis that providing objective, personalised, visual feedback on adherence to patients in combination with a tailored educational intervention in a community pharmacy setting, improves adherence more effectively than education alone. METHODS/DESIGN: The study is a prospective, cluster randomised, parallel-group, multi-site study conducted over 6 months. The study is designed to compare current best practice in care (i.e. routine inhaler technique training) with the use of the INCA® device for respiratory patients in a community pharmacy setting. Pharmacies are the unit of randomisation and on enrolment to the study they will be allocated by the lead researcher to one of the three study groups (intervention, comparator or control groups) using a computer-generated list of random numbers. Given the nature of the intervention neither pharmacists nor participants can be blinded. The intervention group will receive feedback from the acoustic recording device on inhaler technique and adherence three times over a 6-month period along with inhaler technique training at each of these times. The comparator group will also receive training in inhaler use three times over the 6-month study period but no feedback on their habitual performance. The control group will receive usual care (i.e. the safe supply of medicines and advice on their use). The primary outcome is the rate of participant adherence to their inhaled medication, defined as the proportion of correctly taken doses of medication at the correct time relative to the prescribed interval. Secondary outcomes include exacerbation rates and quality of life measures. Differences in the timing and technique of inhaler use as altered by the interventions will also be assessed. Data will be analysed on an intention-to-treat and a per-protocol basis. Sample size has been calculated with reference to comparisons to be made between the intervention and comparator clusters and indicates 75 participants per cluster. With an estimated 10 % loss to follow-up we will be able to show a 20 % difference between the population means of the intervention and comparator groups with a power of 0.8. The Type I error probability associated with the test of the null hypothesis is 0.05. DISCUSSION: This clinical trial will establish whether providing personalised feedback to individuals on their inhaler use improves adherence. It may also be possible to enhance the role of pharmacists in clinical care by identifying patients in whom alteration of either therapy or inhaler device is appropriate. REGISTRATION: ClinicalTrials.gov NCT02203266